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- Title
Autoreactive T effector memory differentiation mirrors β cell function in type 1 diabetes.
- Authors
Yeo, Lorraine; Woodwyk, Alyssa; Sood, Sanjana; Lorenc, Anna; Eichmann, Martin; Pujol-Autonell, Irma; Melchiotti, Rosella; Skowera, Ania; Fidanis, Efthymios; Dolton, Garry M.; Tungatt, Katie; Sewell, Andrew K.; Heck, Susanne; Saxena, Alka; Beam, Craig A.; Peakman, Mark
- Abstract
In type 1 diabetes, cytotoxic CD8+ T cells with specificity for β cell autoantigens are found in the pancreatic islets, where they are implicated in the destruction of insulin-secreting β cells. In contrast, the disease relevance of β cell-reactive CD8+ T cells that are detectable in the circulation, and their relationship to β cell function, are not known. Here, we tracked multiple, circulating β cell-reactive CD8+ T cell subsets and measured β cell function longitudinally for 2 years, starting immediately after diagnosis of type 1 diabetes. We found that change in β cell-specific effector memory CD8+ T cells expressing CD57 was positively correlated with C-peptide change in subjects below 12 years of age. Autoreactive CD57+ effector memory CD8+ T cells bore the signature of enhanced effector function (higher expression of granzyme B, killer-specific protein of 37 kDa, and CD16, and reduced expression of CD28) compared with their CD57- counterparts, and network association modeling indicated that the dynamics of β cell-reactive CD57+ effector memory CD8+ T cell subsets were strongly linked. Thus, coordinated changes in circulating β cell-specific CD8+ T cells within the CD57+ effector memory subset calibrate to functional insulin reserve in type 1 diabetes, providing a tool for immune monitoring and a mechanism-based target for immunotherapy.
- Subjects
TYPE 1 diabetes; CELL physiology; IMMUNOTHERAPY; GRANZYMES; AUTOIMMUNE diseases
- Publication
Journal of Clinical Investigation, 2018, Vol 128, Issue 8, p3460
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI120555